Comprehensive Analysis of the Immune Microenvironment in Checkpoint Inhibitor Pneumonitis
BackgroundWhile immune checkpoint inhibitors (ICIs) are a beacon of hope for non-small cell lung cancer (NSCLC) patients, they can also cause adverse events, including checkpoint inhibitor pneumonitis (CIP). Research shows that the inflammatory immune microenvironment plays a vital role in the devel...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.818492/full |
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| author | Xinqing Lin Xinqing Lin Jiaxi Deng Haiyi Deng Yilin Yang Ni Sun Maolin Zhou Yinyin Qin Xiaohong Xie Shiyue Li Nanshan Zhong Yong Song Yong Song Chengzhi Zhou |
| author_facet | Xinqing Lin Xinqing Lin Jiaxi Deng Haiyi Deng Yilin Yang Ni Sun Maolin Zhou Yinyin Qin Xiaohong Xie Shiyue Li Nanshan Zhong Yong Song Yong Song Chengzhi Zhou |
| author_sort | Xinqing Lin |
| collection | DOAJ |
| description | BackgroundWhile immune checkpoint inhibitors (ICIs) are a beacon of hope for non-small cell lung cancer (NSCLC) patients, they can also cause adverse events, including checkpoint inhibitor pneumonitis (CIP). Research shows that the inflammatory immune microenvironment plays a vital role in the development of CIP. However, the role of the immune microenvironment (IME) in CIP is still unclear.MethodsWe collected a cohort of NSCLC patients treated with ICIs that included eight individuals with CIP (CIP group) and 29 individuals without CIP (Control group). CIBERSORT and the xCell algorithm were used to evaluate the proportion of immune cells. Gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) were used to evaluate pathway activity. The ridge regression algorithm was used to analyze drug sensitivity.ResultsCIBERSORT showed significantly upregulated memory B cells, CD8+ T cells, and M1 Macrophages in the CIP group. The number of memory resting CD4+ T cells and resting NK cells in the CIP group was also significantly lower than in the Control group. The XCell analysis showed a higher proportion of Class-switched memory B-cells and M1 Macrophages in the CIP group. Pathway analysis showed that the CIP group had high activity in their immune and inflammatory response pathways and low activity in their immune exhaustion related pathway.ConclusionsIn this study, we researched CIP patients who after ICIs treatment developed an inflammatory IME, which is characterized by significantly increased activated immune cells and expression of inflammatory molecules, as well as downregulated immunosuppressive lymphocytes and signaling pathways. The goal was to develop theoretical guidance for clinical guidelines for the treatment of CIP in the future. |
| first_indexed | 2024-12-24T23:04:31Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-24T23:04:31Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-08158a23de57477bacf71d139171759f2022-12-21T16:35:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.818492818492Comprehensive Analysis of the Immune Microenvironment in Checkpoint Inhibitor PneumonitisXinqing Lin0Xinqing Lin1Jiaxi Deng2Haiyi Deng3Yilin Yang4Ni Sun5Maolin Zhou6Yinyin Qin7Xiaohong Xie8Shiyue Li9Nanshan Zhong10Yong Song11Yong Song12Chengzhi Zhou13The First School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaThe First School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaBackgroundWhile immune checkpoint inhibitors (ICIs) are a beacon of hope for non-small cell lung cancer (NSCLC) patients, they can also cause adverse events, including checkpoint inhibitor pneumonitis (CIP). Research shows that the inflammatory immune microenvironment plays a vital role in the development of CIP. However, the role of the immune microenvironment (IME) in CIP is still unclear.MethodsWe collected a cohort of NSCLC patients treated with ICIs that included eight individuals with CIP (CIP group) and 29 individuals without CIP (Control group). CIBERSORT and the xCell algorithm were used to evaluate the proportion of immune cells. Gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) were used to evaluate pathway activity. The ridge regression algorithm was used to analyze drug sensitivity.ResultsCIBERSORT showed significantly upregulated memory B cells, CD8+ T cells, and M1 Macrophages in the CIP group. The number of memory resting CD4+ T cells and resting NK cells in the CIP group was also significantly lower than in the Control group. The XCell analysis showed a higher proportion of Class-switched memory B-cells and M1 Macrophages in the CIP group. Pathway analysis showed that the CIP group had high activity in their immune and inflammatory response pathways and low activity in their immune exhaustion related pathway.ConclusionsIn this study, we researched CIP patients who after ICIs treatment developed an inflammatory IME, which is characterized by significantly increased activated immune cells and expression of inflammatory molecules, as well as downregulated immunosuppressive lymphocytes and signaling pathways. The goal was to develop theoretical guidance for clinical guidelines for the treatment of CIP in the future.https://www.frontiersin.org/articles/10.3389/fimmu.2021.818492/fullcheckpoint inhibitor pneumonitisimmune infiltrationimmune microenvironmentaberrant pathway activationimmune check inhibitor (ICI) |
| spellingShingle | Xinqing Lin Xinqing Lin Jiaxi Deng Haiyi Deng Yilin Yang Ni Sun Maolin Zhou Yinyin Qin Xiaohong Xie Shiyue Li Nanshan Zhong Yong Song Yong Song Chengzhi Zhou Comprehensive Analysis of the Immune Microenvironment in Checkpoint Inhibitor Pneumonitis Frontiers in Immunology checkpoint inhibitor pneumonitis immune infiltration immune microenvironment aberrant pathway activation immune check inhibitor (ICI) |
| title | Comprehensive Analysis of the Immune Microenvironment in Checkpoint Inhibitor Pneumonitis |
| title_full | Comprehensive Analysis of the Immune Microenvironment in Checkpoint Inhibitor Pneumonitis |
| title_fullStr | Comprehensive Analysis of the Immune Microenvironment in Checkpoint Inhibitor Pneumonitis |
| title_full_unstemmed | Comprehensive Analysis of the Immune Microenvironment in Checkpoint Inhibitor Pneumonitis |
| title_short | Comprehensive Analysis of the Immune Microenvironment in Checkpoint Inhibitor Pneumonitis |
| title_sort | comprehensive analysis of the immune microenvironment in checkpoint inhibitor pneumonitis |
| topic | checkpoint inhibitor pneumonitis immune infiltration immune microenvironment aberrant pathway activation immune check inhibitor (ICI) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.818492/full |
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